Leveraging molecular targeted drugs and immune checkpoint inhibitors treat advanced thyroid carcinoma to achieve thyroid carcinoma redifferentiation.

Thyroid cancer can be classified into three different types based on the degree of differentiation: well-differentiated, poorly differentiated, and anaplastic thyroid carcinoma. Well-differentiated thyroid cancer refers to cancer cells that closely resemble normal thyroid cells, while poorly differentiated and anaplastic thyroid carcinoma are characterized by cells that have lost their resemblance to normal thyroid cells. Advanced thyroid carcinoma, regardless of its degree of differentiation, is known to have a higher likelihood of disease progression and is generally associated with a poor prognosis. However, the process through which well-differentiated thyroid carcinoma transforms into anaplastic thyroid carcinoma, also known as "dedifferentiation", has been a subject of intensive research. In recent years, there have been significant breakthroughs in the treatment of refractory advanced thyroid cancer. Clinical studies have been conducted to evaluate the efficacy and safety of molecular targeted drugs and immune checkpoint inhibitors in the treatment of dedifferentiated thyroid cancer. These drugs work by targeting specific molecules or proteins in cancer cells to inhibit their growth or by enhancing the body's immune response against the cancer cells. This article aims to explore some of the possible mechanisms behind the dedifferentiation process in well-differentiated thyroid carcinoma. It also discusses the clinical effects of molecular targeted drugs and immune checkpoint inhibitors in thyroid cancer patients with different degrees of differentiation. Furthermore, it offers insights into the future trends in the treatment of advanced thyroid cancer, highlighting the potential for improved outcomes and better patient care.

Adalimumab in Treating Refractory Livedoid Vasculopathy.

Livedoid vasculopathy is a chronic, recurrent skin disorder. It seriously affects the quality of patients' life. However, the pathogenesis has not been fully identified yet. Here, this retrospective study describes the successful use of anti-TNF-α agent adalimumab in three cases of refractory livedoid vasculopathy, which has not been reported previously. In addition, we provide some clinical evidence that adalimumab therapy is efficient in improving skin lesions and relieving the pain of livedoid vasculopathy.

Pediatric asthma control during the COVID-19 pandemic: A systematic review and meta-analysis.

BACKGROUND: With the onset of the coronavirus disease 2019 (COVID-19) pandemic, many experts expected that asthma-associated morbidity because of severe acute respiratory syndrome coronavirus 2 infection would dramatically increase. However, some studies suggested that there was no apparent increasing in asthma-related morbidity in children with asthma, it is even possible children may have improved outcomes. To understand the relationship between the COVID-19 pandemic and asthma outcomes, we performed this article. METHODS: We searched PubMed, Embase, and Cochrane Library to find literature from December 2019 to June 2021 related to COVID-19 and children's asthma control, among which results such as abstracts, comments, letters, reviews, and case reports were excluded. The level of asthma control during the COVID-19 pandemic was synthesized and discussed by outcomes of asthma exacerbation, emergency room visit, asthma admission, and childhood asthma control test (c-ACT). RESULTS: A total of 22,159 subjects were included in 10 studies. Random effect model was used to account for the data. Compared with the same period before the COVID-19 pandemic, asthma exacerbation reduced (odds ratio [OR] = 0.26, 95% confidence interval [CI] = [0.14-0.48], Z = 4.32, p < 0.0001), the odds of emergency room visit decreased as well (OR = 0.11, 95% CI = [0.04-0.26], Z = 4.98, p < 0.00001). The outcome of asthma admission showed no significant difference (OR = 0.84, 95% CI = [0.32-2.20], Z = 0.36, p = 0.72). The outcome of c-ACT scores were not analyzed because of the different manifestations used. Overall, c-ACT scores reduced during the pandemic. CONCLUSION: Compared to the same period before the COVID-19 pandemic, the level of asthma control has been significantly improved. We need to understand the exact factors leading to these improvements and find methods to sustain it.

Zinc Oxide Nanoparticles Prime a Protective Immune Response in Galleria mellonella to Defend Against Candida albicans.

Purpose: Zinc oxide nanoparticles (ZnO-NPs) have exerted antimicrobial properties. However, there is insufficient evaluation regarding the in vivo antifungal activity of ZnO-NPs. This study aimed to investigate the efficacy and mechanism of ZnO-NPs in controlling Candida albicans in the invertebrate Galleria mellonella. Methods: Galleria mellonella larvae were injected with different doses of ZnO-NPs to determine their in vivo toxicity. Non-toxic doses of ZnO-NPs were chosen for prophylactic injection in G. mellonella followed by C. albicans infection. Then the direct in vitro antifungal effect of ZnO-NPs against C. albicans was evaluated. In addition, the mode of action of ZnO-NPs was assessed in larvae through different assays: quantification of hemocyte density, morphology observation of hemocytes, characterization of hemocyte aggregation and phagocytosis, and measurement of hemolymph phenoloxidase (PO) activity. Results: Zinc oxide nanoparticles were non-toxic to the larvae at relatively low concentrations (≤20 mg/kg). ZnO-NP pretreatment significantly prolonged the survival of C. albicans-infected larvae and decreased the fungal dissemination and burden in the C. albicans-infected larvae. This observation was more related to the activation of host defense rather than their fungicidal capacities. Specifically, ZnO-NP treatment increased hemocyte density, promoted hemocyte aggregation, enhanced hemocyte phagocytosis, and activated PO activity in larvae. Conclusion: Prophylactic treatment with lower concentrations of ZnO-NPs protects G. mellonella from C. albicans infection. The innate immune response primed by ZnO-NPs may be part of the reason for the protective effects. This study provides new evidence of the capacity of ZnO-NPs in enhancing host immunity and predicts that ZnO-NPs will be attractive for further anti-infection applications.

Clinical Effectiveness of Intravenous Peramivir Compared With Oseltamivir in Patients With Severe Influenza A With Primary Viral Pneumonia: A Randomized Controlled Study.

BACKGROUND: High-quality evidence confirms that the clinical efficacy of peramivir in severe influenza patients with primary viral pneumonia is lacking. To optimize clinical medication, we evaluate the different efficacy between peramivir and oseltamivir in the treatment of severe influenza A with primary viral pneumonia. METHODS: A single-center, randomized, controlled trial was conducted during the Chinese influenza season from December 2018 to April 2019 in patients with severe influenza A with primary viral pneumonia. A total of 40 inpatients were enrolled and treated with either intravenous peramivir (300 mg, once daily for 5 days) or oral oseltamivir (75 mg, twice daily for 5 days). RESULTS: The duration of influenza virus nucleic acid positivity in the oseltamivir group and the peramivir group was 2.95 days and 2.80 days, respectively. The remission times of clinical symptoms in the oseltamivir group and the peramivir group were 3.90 days and 3.25 days, respectively. In addition, the remission time of cough symptoms in the peramivir group (63.89 hours) was shorter than that in the oseltamivir group (75.53 hours). There was no significant difference between these values (P > .05). The remission time of fever symptoms in the oseltamivir group was 23.67 hours, which was significantly longer than that in the peramivir group (12.32 hours) (P = .034). CONCLUSIONS: Peramivir is no less effective than oseltamivir in the treatment of severe influenza A with primary viral pneumonia, and patients treated with peramivir had significantly shorter remission times of fever symptoms than those treated with oseltamivir.

Pre-exposure to Candida glabrata protects Galleria mellonella against subsequent lethal fungal infections.

Commensal fungi are an important part of human microbial community, among which Candida albicans and Candida glabrata are two common opportunistic pathogens. Unlike the high pathogenicity of C. albicans, C. glabrata is reported to show low pathogenicity to the host. Here, by using a Galleria mellonella infection model, we were able to confirm the much lower virulence of C. glabrata than C. albicans. Interestingly, pre-exposure to live C. glabrata (LCG) protects the larvae against subsequent various lethal fungal infections, including C. albicans, Candida tropicalis, and Cryptococcus neoformans. Inconsistently, heat-inactivated C. glabrata (HICG) pre-exposure can only protect against C. albicans or C. tropicalis re-infection, but not C. neoformans. Mechanistically, LCG or HICG pre-exposure enhanced the fungicidal activity of hemocytes against C. albicans or C. tropicalis. Meanwhile, LCG pre-exposure enhanced the humoral immunity by modulating the expression of fungal defending proteins in the cell-free hemolymph, which may contribute to the protection against C. neoformans. Together, this study suggests the important role of C. glabrata in enhancing host immunity, and demonstrates the great potential of G. mellonella model in studying the innate immune responses against infections.

Photodynamic therapy combined with surgical management of extensive anogenital condylomatosis in a patient with systemic lupus erythematosus.

Infections with human papillomavirus in the anogenital area result in warty, papillary, and condylomatous lesions. The giant anogenital wart is relatively uncommon. Treatment of giant wart is challenging, especially in the immunosuppressive population. Here, a patient with systemic lupus erythematosis had extensive, fast-growing, recurrent anogenital condylomatosis shaped as giant cauliflowers. We reported this case and the successful treatment of photodynamic therapy combined with surgical management. It provided the feasibility for surgical ablation combined with ALA-PDT performed for these kinds of challenging cases.

A Retrospective Analysis of Three Antiviral Regimens of Peramivir in the Treatment of Severe Influenza A with Primary Viral Pneumonia.

Objective: To evaluate the difference of clinical efficacy of peramivir alone and peramivir combined with immunomodulators (either ribonucleic acid or thymopetidum) in the treatment of severe influenza A with primary viral pneumonia. Methods: A retrospective analysis was applied to 45 patients who were diagnosed with severe influenza A with primary viral pneumonia in our hospital from December 2017 to March 2018. The cases were divided into three groups: the peramivir group, the peramivir combined with ribonucleic acid group, and the peramivir combined with thymopetidum group. Results: The duration of viral nucleic acid positivity in the peramivir group, the peramivir combined with ribonucleic acid group, and the peramivir combined with thymopetidum group was 6.13 ± 2.06, 6.53 ± 2.72, and 6.10 ± 1.37 days, respectively. The remission time of the clinical symptoms of the peramivir group, the peramivir combined with ribonucleic acid group, and the peramivir combined with thymopetidum group was 8.06 ± 2.73, 7.94 ± 2.89, and 7.67 ± 1.58 days, respectively. Comparisons between the peramivir group and the peramivir combined with ribonucleic acid group or the peramivir combined with thymopetidum group revealed no significant differences in the duration of virus nucleic acid positivity, remission time of clinical symptoms, time to fever alleviation, and time to cough alleviation. Conclusions: There is no observed benefit in the addition of ribonucleic acid or thymopetidum when peramivir sodium chloride injection is used in the treatment of severe influenza A with primary viral pneumonia. This trial is registered with ChiCTR1800019417.

Polymorphism analyses of 19 STRs in Labrador Retriever population from China and its heterozygosity comparisons with other retriever breeds.

Pure breed dogs of Western origin are increasingly more popular in China as is a need to differentiate breeds and individual dogs for personal and forensic reasons. Research on genetic diversities of the canine population in China is rarely conducted. In this study, genetic distributions and forensic efficiencies of 19 canine STR loci in Labrador Retriever population from China were evaluated by using one available commercial canine kit in China. This panel was used to genetically define 214 Labrador Retrievers in China, as an example of one of the most important Western breeds and to compare them with Labrador Retrievers from America based on three overlapping STR loci. Moreover, genetic relationship analyses between Labrador Retriever population and two reference populations in America were performed. All 19 STR loci were polymorphic and conformed to Hardy-Weinberg equilibrium in the studied population. The STR panel was able to discern individual dogs with a high degree of accuracy. Breed-wide genetic heterozygosity comparisons based on present and published allele frequencies revealed that the studied population had the lower genetic heterozygosity than canine populations in America. Principal component analysis among Labrador Retriever population and other reference populations showed that the studied Labrador Retrievers were genetically close to the retriever breeds in America. Population genetic structure analyses among these canine breeds further revealed genetic differentiations between the studied Labrador Retriever population and other compared breeds. In conclusion, these STR loci had relatively high forensic values in Labrador Retriever population in China, which could be employed for individual identification and kinship testing.

Evaluation of the MiSeq FGx system for use in forensic casework.

Capillary electrophoresis (CE) is widely used in forensic genetics to study short tandem repeats (STRs). Recently, next-generation sequencing (NGS) platforms have facilitated the development of new strategies for forensic DNA typing. Several studies have shown that NGS successfully analyzes challenging samples. However, because NGS is complicated and time-consuming, it remains unclear whether NGS platforms offer significant advantages over CE for all forensic cases. Here, the MiSeq FGx system was used to test some cases that had previously been analyzed using CE. These cases included paternity test cases in which some samples exhibited locus inconsistencies; samples with off-ladder (OL) alleles; samples with triallelic patterns; and samples with amelogenin test abnormalities. The results generated by MiSeq FGx were compared to those previously generated by CE. The MiSeq FGx and CE results were consistent with the exception of three samples, where inconsistencies were observed at the Penta D locus. For all three incongruent samples, the MiSeq FGx results were correct. Sequence analysis indicated that, in two cases, mismatches were due to undetected alleles rather than mutations. In two additional cases, mutation sources were identified, and in a fifth case, mutation step size was reconsidered. MiSeq FGx was used to identify OL alleles and samples with amelogenin test abnormalities. For cases where verification was required via CE analysis, the simultaneous NGS amplification of several types of multiple genetic markers improved testing efficiency. In addition, we identified additional sequence variants at autosomal, Y chromosomal, and X chromosomal STR loci in the Han Chinese population from northern China. Our results will be useful for future forensic analyses of STR genotypes in Chinese populations. It is likely that NGS would be more widely used in forensic genetics if costs and procedure complexity were reduced.

[Metabolic and excretory process of Citri Reticulatae Pericarpium Viride and Citri Reticulatae Pericarpium in rats' urine and feces analyzed by RRLC-QqQ-MSn].

This present study was to investigate the metabolism and excretion of characteristic polyphenols such as flavonoids and coumarins in urine and feces of rats after intragastric administration of ethanol extracts of Citri Reticulatae Pericarpium Viride and Citri Reticulatae Pericarpium. The urine and feces of rats were collected after intragastric administration of 70% ethanol extracts of Citri Reticulatae Pericarpium Viride and Citri Reticulatae Pericarpium. Rapid resolution liquid chromatography coupled with quadrupole tandem mass spectrometry (RRLC-QqQ-MSn) was applied to compare the contents of polyphenols in ethanol extract, urine and feces. By comparing with reference substance, 30 polyphenols were identified from the ethanol extracts of Citri Reticulatae Pericarpium Viride and Citri Reticulatae Pericarpium, including flavone glycosides, flavones, flavonone glycosides, flavonones, flavonol glycosides, polymethoxyflavones, coumarins, and limonoids and so on. The detection of various types of compounds showed differences in contents between the intestinal metabolism and excretion in the feces after systemic circulatory metabolism and renal excretion. The results showed that the polymethoxyflavones and flavonones were primarily excreted through urine, and the flavonone glycosides and limonoids were primarily excreted through feces. However, coumarins were hardly detected in feces and urine, indicating that coumarins may be metabolized in the body.

[Particle Size Distribution and Human Health Risk Assessment of Heavy Metals in Atmospheric Particles from Beijing and Xinxiang During Summer].

Under a condition of good air quality (AQI:55-90, PM10:37-97 µg·m-3, PM2.5:17-76 µg·m-3), six groups of 54 samples were collected using an Andersen cascade impactor from both the indoor and outdoor stations in Beijing and Xinxiang from June to August in 2016. The samples were digested by microwave digestion, and nine heavy metal elements (Pb, Cr, Ni, Cu, Zn, As, Cd, Mn, and Co) in the atmospheric particles were determined with an inductively coupled plasma source mass spectrometer (ICP-MS). The results showed that the enrichment index (0-3) of most elements were low in both cities except for Cd[15.0 (Beijing) and 8.47 (Xinxiang)]. Cr, Co, Cu, and Mn in the atmospheric particles from Beijing park, Cd, Pb, and Mn in the atmospheric particles from the Beijing office, Cr, Co, Ni, and As in the atmospheric particles from Xinxiang park, and all nine heavy metal elements in the atmospheric particles from roads in both cities were found to be more concentrated in the coarse fractions; however, Pb, Zn, Cd, Ni, and As in the atmospheric particles from Beijing park, Co, Zn, Ni, Cr, As, and Cu in the atmospheric particles from the Beijing office, Pb, Zn, Cd, Cu, and Mn in the atmospheric particles from Xinxiang park, and all nine metal elements in the atmospheric particles from the Beijing office showed the opposite pattern. The result of a human health risk assessment indicated that the carcinogenic risk of the five carcinogenic elements were all less than 10-4, but a lower potential cancer risk would also occur under long term exposure. For the four non-carcinogenic elements (Pb, Zn, Mn, and Cu), the non-carcinogenic health risk values of Pb, Zn, Mn, and Cu in the atmospheric particulates in Beijing were all far less than 1, which means the corresponding non-carcinogenic risk was negligible; and, except for Mn, there was no obvious non-carcinogenic risk from Pb, Zn, and Cu in the atmospheric particles of Xinxiang.

Peroxisome proliferator-activated receptor-γ agonist-mediated inhibition of cell growth is independent of apoptosis in human epidermoid carcinoma A431 cells.

Evidence suggests that peroxisome proliferator activated receptor-γ (PPAR-γ) acts as a tumor suppressor in multiple types of cancer; however, the role of action of PPAR-γ on human epidermoid carcinoma is unclear. The present study investigated the effects of a PPAR-γ agonist, rosiglitazone, on human epidermoid carcinoma cell growth using the A431 cell line. The effects of rosiglitazone on cell viability and proliferation were evaluated with MTS and [3H] thymidine incorporation assays. The effects of rosiglitazone on the cell cycle and apoptosis were analyzed by flow cytometry, and western blotting. It was identified that rosiglitazone inhibited A431 cell proliferation in a dose-dependent manner, increased the proportion of cells in the G1 phase, but did not affect apoptosis. Consistently, there was a significant decrease in the expression of cell proliferation-associated proteins, including cyclin D1, cyclin-dependent kinase (Cdk)2 and Cdk4 in A431 cells treated with rosiglitazone. This decrease was rescued by a selective antagonist of PPAR-γ or specific PPAR-γ small interfering RNAs. However, the ratio of B-cell lymphoma 2 (Bcl-2) to Bcl-2 associated X protein, which is associated with cell apoptosis, was not affected by these treatments. The data of the present study suggest that the PPAR-γ agonist rosiglitazone inhibits human epidermoid carcinoma cell growth through regulating the expression of the cell cycle-associated proteins, and that this effect is independent of apoptosis.

Chemotaxonomic Classification Applied to the Identification of Two Closely-Related Citrus TCMs Using UPLC-Q-TOF-MS-Based Metabolomics.

This manuscript elaborates on the establishment of a chemotaxonomic classification strategy for closely-related Citrus fruits in Traditional Chinese Medicines (TCMs). UPLC-Q-TOF-MS-based metabolomics was applied to depict the variable chemotaxonomic markers and elucidate the metabolic mechanism of Citrus TCMs from different species and at different ripening stages. Metabolomics can capture a comprehensive analysis of small molecule metabolites and can provide a powerful approach to establish metabolic profiling, creating a bridge between genotype and phenotype. To further investigate the different metabolites in four closely-related Citrus TCMs, non-targeted metabolite profiling analysis was employed as an efficient technique to profile the primary and secondary metabolites. The results presented in this manuscript indicate that primary metabolites enable the discrimination of species, whereas secondary metabolites are associated with species and the ripening process. In addition, analysis of the biosynthetic pathway highlighted that the syntheses of flavone and flavone glycosides are deeply affected in Citrus ripening stages. Ultimately, this work might provide a feasible strategy for the authentication of Citrus fruits from different species and ripening stages and facilitate a better understanding of their different medicinal uses.

[Distribution of podophyllotoxin-loaded nanostructured lipid carriers after topical application on cervical mucosa in Tibet minipigs].

OBJECTIVE: To assess the distribution and systemic toxicity of podophyllotoxin-loaded nanostructured lipid carriers (POD-NLC) after topical application on the cervical mucosa in Tibet minipigs. METHODS: Twelve Tibet mini-pigs were randomized into test group and control group to receive topical application of 0.5% POD-NLC and 0.5% POD tincture, respectively, on the cervical mucosa. Cervical mucosal irritation, targeted distribution and systemic absorption of POD were observed at different time points within 24 h after the drug application. RESULTS: No local inflammation reaction was observed in the test group, while serious local irritations (swelling, blisters, blood blisters, erosion and ulceration) occurred in the control group. The fluorescence intensity of POD in the mucosal tissue reached the peak level at 4 h after drug application in the control group, while the POD fluorescence intensity increased slowly and reached the peak level at 16 h in the test group. The peak blood POD concentration occurred at 6 h after POD-NLC application in the test group (14.28∓0.33 ng/mL), as compared to 4 h in the control group (42.46∓0.32 ng/mL). At all the time points within 24 h, blood POD concentration remained significantly lower in the test group than in the control group (P<0.05), and the area under curve of blood POD concentration in the control group was 1.38-fold greater than that in the test group. CONCLUSION: POD-NLC allows sustained release of POD and achieves a higher POD concentration in the mucosal tissue without causing local irritation or obvious systemic toxicity in Tibet minipigs.

[Particle Size Distribution, Seasonal Variation Characteristics and Human Exposure Assessment of Heavy Metals in Typical Settled Dust from Beijing].

Four types of dust from dormitories, offices, hotels and roads in Beijing were collected and fractionated into 9 fractions, respectively. Totally 36 samples were obtained and analyzed for heavy metals including Cu, Zn, Cr, Pb, Cd and Ni. Particle size distributions of those heavy metals in these four types of dust were investigated and the influencing mechanisms were discussed. Distribution patterns of the same heavy metal in different types of dust showed various characteristics. Also different metals in the same type of dust represented different distribution patterns. Heavy metals in road dust tended to concentrate in finer particles. Two offices from the same building, located in Beijing, China, were selected to study the seasonality of heavy metals in dust. Dust sampling from Office A was conducted at weekly intervals between March 2012 and August 2012, while dust from Office B was sampled fortnightly from March 2012 to December 2012. Generally, levels of all heavy metals remained stable among different seasons, however, Cr and Pb represented more significant fluctuations than other four heavy metals. Based on the geo-accumulation index method, the pollution of Zn, Cu and Pb was more serious in the investigated samples, and dust from offices and hotels were moderately polluted by Zn. According to the risk assessment results, the carcinogenic health risks of the six heavy metals in the four types of dust were negligible.

[Study on HPLC fingerprint and chemical constituent difference of different species of Aurantii Fructus Immaturus].

This study is to establish an HPLC fingerprint by HPLC-DAD method and simultaneous quantitative analysis of 17 components of 18 batches of Citrus aurantium and 10 batches of C. sinensis. The separation was performed on an Agilent Poroshell 120 SB-C18 (4.6 mm×100 mm,2.7 µm) column with the gradient elution of methanol-0.1% formic acid water, the flow was 0.6 mL•min⁻¹. The detection wavelength was set at 318 nm. The column temperature was maintained at 30 ℃. The data calculation was performed with similarity evaluation system for chromatographic fingerprint of traditional Chinese medicine (Version 2004A) together with SIMCA-P 13.0 software to clarify the differential marker between these two different species of Aurantii Fructus Immaturus. This method has good precision stability and repeatability that could provide basis for quality control and evaluation of Aurantii Fructus Immaturus.

[Genetic polymorphisms of 16 STR loci in Tibetan Mastiff].

OBJECTIVE: To explore the genetic polymorphisms of 16 STR loci from 449 Tibetan Mastiffs in order to set up gene polymorphism database of Tibetan Mastiff. METHODS: The PCR amplification was performed using the 16 STR loci fluorescent multiple amplification kit for dog. The amplified products were detected and statistically analyzed. RESULTS: In the 16 STR loci from 449 Tibetan Mastiffs, CDP was 0.999 999 999 999 999 and CEP was 0.999 997 795. Except FH2010 (10 alleles), PEZ21 (12 alleles), and PEZ05 (13 alleles), the other STR loci had more than 15 alleles. In the 16 STR loci, H was > 0.5 and PIC was > 0.7. CONCLUSION: The 16 STR loci have high polymorphism to be suitable for individual identification and paternity testing of Tibetan Mastiff. The data obtained through this study can be used to establish DNA polymorphism database of Tibetan Mastiff.